CD34+CD38+CD19+ as well as CD34+CD38-CD19+ cells are leukemia-initiating cells with self-renewal capacity in human B-precursor ALL

被引：128

作者：

Kong, Y. ^{[2
,3
]}

Yoshida, S. ^{[2
]}

Saito, Y.

Doi, T.

Nagatoshi, Y. ^{[4
]}

Fukata, M. ^{[2
]}

Saito, N. ^{[2
]}

Yang, S. M. ^{[3
]}

Iwamoto, C. ^{[2
]}

Okamura, J. ^{[4
]}

Liu, K. Y. ^{[3
]}

Huang, X. J. ^{[3
]}

Lu, D. P. ^{[3
]}

Shultz, L. D. ^{[5
]}

Harada, M.

Ishikawa, F. ^{[1
]}

机构：

[1] RIKEN RCAI, Res Unit Human Dis Models, Tsurumi Ku, Kanagawa 2300045, Japan

[2] Kyushu Univ, Grad Sch Med Sci, Dept Med & Biosyst Sci, Fukuoka 812, Japan

[3] Peking Univ, Peoples Hosp, Inst Hematol, Beijing 100871, Peoples R China

[4] Kyushu Natl Canc Ctr, Dept Pediat, Fukuoka, Japan

[5] Jackson Lab, Bar Harbor, ME 04609 USA

来源：

LEUKEMIA | 2008年 / 22卷 / 06期

基金：

美国国家卫生研究院;

关键词：

acute lymphocytic leukemia; stem cells; transplantation;

D O I：

10.1038/leu.2008.83

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The presence of rare malignant stem cells supplying a hierarchy of malignant cells has recently been reported. In human acute myelogenous leukemia (AML), the leukemia stem cells (LSCs) have been phenotypically restricted within the CD34+CD38- fraction. To understand the origin of malignant cells in primary human B-precursor acute lymphocytic leukemia (B-ALL), we established a novel in vivo xenotransplantation model. Purified CD34+CD38+CD19+, CD34+CD38-CD19+ and CD34+CD38-CD19- bone marrow ( BM) or peripheral blood (PB) cells from three pediatric B-ALL patients were intravenously injected into sublethally irradiated newborn NOD/SCID/IL2r gamma(null) mice. We found that both CD34+CD38+CD19+ and CD34+CD38-CD19+ cells initiate B-ALL in primary recipients, whereas the recipients of CD34+CD38-CD10-CD19- cells showed normal human hematopoietic repopulation. The extent of leukemic infiltration into the spleen, liver and kidney was similar between the recipients transplanted with CD34+CD38+CD19+ cells and those transplanted with CD34+CD38-CD19+ cells. In each of the three cases studied, transplantation of CD34+CD38+CD19+ cells resulted in the development of B-ALL in secondary recipients, demonstrating self-renewal capacity. The identification of CD34+CD38+ CD19+ self-renewing B-ALL cells proposes a hierarchy of leukemia-initiating cells (LICs) distinct from that of AML. Recapitulation of patient B-ALL in NOD/SCID/IL2r gamma(null) recipients provides a powerful tool for directly studying leukemogenesis and for developing therapeutic strategies.

引用

页码：1207 / 1213

页数：7

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